This NIMH Mentored Patient-Oriented Research Career Development application is to support Dr. Melissa DelBello's long-term career objective of developing expertise integrating innovative neuroimaging techniques and longitudinal outcome studies to understand the neurodevelopment of Bipolar Disorder (BPD). The candidate's previous training is in Magnetic Resonance Imaging (MRI) morphometric analyses and the phenomenology of BPD. One limitation of previous neuroimaging studies has been inadequate assessment of illness course, thereby limiting the interpretability of imaging findings. Therefore, in order to achieve her career goals and maximize the clinical interpretability of the imaging data, the candidate proposes to gain expertise integrating longitudinal outcome studies, functional MRI (fMRI), statistical analyses, and the ethical conduct of research by participating in course work, didactic readings, mentoring, and experiential learning activities, which complement the proposed research activities. BPD is a common, life-long, progressive disease that typically begins in adolescence or early adulthood and is associated with significant morbidity and mortality. Two of the cardinal symptoms of BPD are dysfunction of attention and emotional regulation. Anterior limbic brain regions, including the prefrontal cortex, thalamus, striatum, amygdala, and cerebellar vermis have been shown to modulate attention and emotional processes. Previous neuroimaging studies, reports of secondary mania, and pilot work, have implicated abnormalities in anterior limbic brain regions in the neurophysiology of BPD. Therefore, the candidate's short-term goal is to apply fMRI in conjunction with longitudinal assessments to clarify the neurophysiological basis for attentional and emotional dysfunction in adolescents with BPD. We hypothesize that anterior limbic abnormalities underlie the attentional and emotional dysfunction in adolescents with BPD. Moreover, we hypothesize that abnormalities in anterior limbic brain regions are associated with increased mood cycling and poor illness outcome. These hypotheses will be examined by studying fMRI regional brain activation associated with tasks of attention and facial affect recognition in adolescents with BPD. Additionally, we will assess structural brain abnormalities in first-hospitalization manic BPD adolescents and associated outcome. The proposed integrated research and training programs, together with the productive research environments of the Bipolar and Psychotic Disorders Research Program at the University of Cincinnati College of Medicine and the Children's Hospital Medical Center's Imaging Research Center, will foster the candidate's development into an independent investigator in the field of the neurodevelopment of BPD. The research conducted will advance our understanding of the neurophysiology of BPD.